Top News for World Encephalitis Day

In recent months, the NeurologyLive® team has been covering the news and conducting interviews with experts on the latest updates in the clinical care of individuals with encephalitis including those with autoimmune encephalitis (AE). Autoimmune encephalitis is a rare, complex disease that where the body’s immune system attacks healthy cells and tissues to the brain or spinal cord.

For World Encephalitis Day— February 22, 2023—the team has culminated some of the biggest pieces of news and insightful exchanges with physicians to offer updates on new developments in literature and expert opinions about autoimmune encephalitis to spread awareness on the prevention and treatment of the condition.

Click here for more coverage of the latest encephalitis related news from NeurologyLive®.

Expert Insights

To understand more about the approach to treating AE, as well as understanding different presentations of the disease, NeurologyLive® sat down with Sean Pittock, MD. Pittock, director of Mayo’s Center for Multiple Sclerosis and Autoimmune Neurology, discussed the numerous complications patients with AE face and why each case presents a different challenge. He also discussed the importance of biomarker testing, clinical and historical examinations to limit incorrect diagnoses.

Amy Kunchok, MD, staff neurologist, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, disscussed the age and sex associations of autoimmune/paraneoplastic biomarkers and how it may aid in the prognostication and provide inference to disease pathophysiology. NeurologyLive® sat down with Kunchok at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2022, Feb 24-26, in West Palm Beach, Florida, to discuss why this is an important area of research, along with some of the specific findings she observed.¹ Additionally, she provided insight on which findings may contrast what has been previously known about autoimmune disorders.

Divyanshu Dubey, MBBS, an assistant professor of neurology at Mayo Clinic, presented an invited talk at ACTRIMS Forum 2021, February 25–27, about autoimmune encephalitis. In the interview, he detailed the greatest unmet needs in treating this disease, and the steps necessary to better controlling it. Corticosteroids and other immunosuppressive medications are typically used to control the inflammation in the brain. Despite these options, there remains about 40% to 50% of autoimmune encephalitis cases that are not revealed through biomarkers, according to Dubey.

Latest Literature

EEG Changes in Acute Phase of Autoimmune Encephalitis May Predict Risk of Drug-Resistant Epilepsy

In a recent retrospective analysis, drug-resistant epilepsy (DRE) was found to be uncommon in patients with AE at 12-month follow-up, but was associated with several risk factors, including the presence of status epilepticus (SE) during acute admission and multiple biomarkers of neuronal dysfunction on electroencephalography (EEG).²

The first objective of the study, identifying the prevalence of DRE, was observed in 16% (n = 11) of the 69-patient cohort who were retrospectively followed up at 12 months. Using EEG data gathered at admission, investigators found the presence of SE (OR, 11.50; 95% CI, 2.81-51.86; P <.001), temporal lobe focality (OR, 9.90; 95% CI, 2.60-50.71; P = .001) and periodic discharges (OR, 19.12; 95% CI, 3.79-191.10; P = .001) were associated with the development of DRE.

At 12 months, 33% (n = 23) were seizure-free but still on antiseizure medications (ASMs), 48% (n = 33) were seizure-free while off of ASMs, and 19% (n = 13) had ongoing seizures. SE was reportedly more likely to occur in seronegative patients (63%), while DRE was prevalent across most subtypes aside from LGI-1 (0%).

Tofacitinib Shows Potential as Therapeutic Option for CNS Autoimmune Diseases

Findings published from a retrospective study evaluating the off-label use of tofacitinib (Xeljanz; Pfizer) in a small cohort of patients with refractory autoimmune encephalitis suggest there may be potential for the drug as a therapeutic.³

Among a cohort of 8 patients treated with tofacitinib, 2 (25%; patients 1 and 8) had good responses, 3 (37.5%; patients 3, 5, and 6) had partial response, and the other 3 (37.5%; patients 2, 4, and 7) had no response. Good response was defined as having Clinical Global Impression score (CGI-I) of 1, whereas scores of 3 and 4 represented partial and no responses to treatment, respectively.

Tofacitinib has previously shown to penetrate the blood-brain barrier (BBB) and is effective against refractory immune-mediated diseases, such as rheumatoid arthritis, psoriasis, and ulcerative colitis. The drug received FDA approval to treat rheumatoid arthritis in 2012, and later gained approvals to treat active psoriatic arthritis, severely active ulcerative colitis, and active polyarticular course juvenile idiopathic arthritis in 2017 and 2018, respectively.⁴

REFERENCES
1. Kunchok, A, McKeon A, Zekeridou A, et al. Autoimmune encephalitis antibody biomarkers: frequency, age and sex associations. Presented at: ACTRIMS Forum 2022; February 24-26; West Palm Beach, Florida. Abstract CE2.4
2. Wesselingh R, Broadley J, Buzzard K, et al. Prevalence, risk factors, and prognosis of drug-resistant epilepsy in autoimmune encephalitis.Epilep & Behav. 2022;132:108729. doi:10.1016/j.yebeh.2022.108729.
3. Jang Y, Lee WJ, Lee HS, Chu K, Lee SK, Lee ST. Tofacitinib treatment for refractory autoimmune encephalitis. Epilepsia. Published online March 3, 2021. doi: 10.1111/epi.16848
4. Xeljanz, Xeljanz XR (tofacitinib): drug safety communication – initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine. News release. FDA. February 4, 2021. Accessed February 21, 2023. https://www.fda.gov/safety/medical-product-safety-information/xeljanz-xeljanz-xr-tofacitinib-drug-safety-communication-initial-safety-trial-results-find-increased#:~:text=In%202018%2C%20FDA%20approved%20the,%2C%20PsA%2C%20and%20ulcerative%20colitis.